The present invention relates to a series of new octahydronaphthalene oxime derivatives, which have the ability to inhibit the biosynthesis of cholesterol. The invention also provides methods and compositions using these compounds as well as processes for preparing them. A number of compounds which may be generally described as 7-[substituted 1,2,3,5,6,7,8,8a-octahydro-1-naphthyl]-3,5-dihydroxyheptanoates is known, of which the closest are thought to be those compounds having the formula (A): ##STR2## (in which A, R, X and Y are essentially as defined hereafter in relation to the compounds of the present invention). These compounds are disclosed, inter alia, in European Patent Publication No. 314 435, which also describes in greater detail than herein the development and forerunners of these types of compound. These compounds of formula (A) are believed by us to be the closest compounds to those of the present invention. These prior art compounds, like the compounds of the present invention, have the ability to inhibit the biosynthesis of cholesterol, and can thus be used for the treatment and prophylaxis of the various diseases caused by hypercholesterolemia, such as atherosclerosis and various cardiac disorders.
Other, similar, classes of compounds, which also have some resemblances to the compounds of the present invention are those compounds have been described in Japanese Patent Kokai Application, No. Sho 60-123445 (European Patent Publication No. 142 146) and Journal of Medicinal Chemistry 32, 197 (1989). They may be represented by the formulae (B) and (C): ##STR3## in which: E represents a group of formula --CH.sub.2 CH.sub.2 --, --CH.dbd.CH-- or --(CH.sub.2).sub.3 --; A.sup.1 represents a hydrogen atom or a lower alkyl group; A.sup.2 represents a lower alkyl group; A.sup.3 represents a hydrogen atom or a methyl group; and A.sup.4, A.sup.5 and A.sup.6, which are the same as each other or different from each other, each represents a hydrogen atom, a halogen atom, a lower alkyl group or an unsubstituted phenyl group.
Compounds corresponding to these compounds of formula (B) and (C) but having a hydroxy group at the 5-position in place of the 5-oxo group are also known. They are known to have an ability to inhibit the biosynthesis of cholesterol which is consistently greater then that of the corresponding 5-oxo compounds.
We have now surprisingly found that the 5-oxo compounds corresponding to the 5-hydroxy compounds of formula (A) have a significantly greater cholesterol biosynthesis inhibitory activity than do the 5-hydroxy compounds of formula (A).